Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS: The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.

Single agent 2',2'-difluorodeoxycytidine in the treatment of metastatic urothelial carcinoma: a phase II study.

PURPOSE: To evaluate the therapeutic activity and toxicity of gemcitabine in the treatment of metastatic urothelial carcinoma. PATIENTS AND METHODS: Twenty-four consecutive patients with recurrent- and/or metastatic urothelial carcinoma pretreated with first line cisplatin-based chemotherapy were treated with gemcitabine 1000 mg/m2/week intravenously diluted in 250 cc of normal saline as 20 minutes infusion for 3 consecutive weeks followed by a 1 week rest period. Chemotherapy was repeated every 28 days. RESULTS: All enrolled patients were evaluable for objective response accordingly to an intent-to-treat analysis. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 7.4+ months (range 3.0+/12.8). Six patients showed no changes (25%) with a median duration of 4.0 months. A subjective improvement in tumor-related symptoms was reported by all responding patients, and in 3 patients with no change. Six out of 9 patients with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 76 cycles (a mean of 3.1 cycles/patient), grade 1-2 leukopenia was seen in 9 patients (37%), grade 1-2 thrombocytopenia in 4 patients (17%), and grade 1 anemia in only 2 cases (8%). Grade 3 leukopenia was seen in 3 cases (12.5%). Grade 4 leukopenia or grade 3-4 thrombocytopenia were not seen. Gastrointestinal toxicity was very mild. CONCLUSIONS: Single agent gemcitabine at the dose of 1000 mg/m2 on a weekly schedule is active, at least in terms of objective response rate and tumor-related symptoms palliation, against pretreated urothelial carcinoma with good tolerability. These results compare favorably with those achieved with the most active drugs such as cisplatin and methotrexate.

Subcutaneous low-dose interleukin-2 and intravenous 5-fluorouracil plus high-dose levofolinic acid as salvage treatment for metastatic colorectal carcinoma.

Thirty-three consecutive patients with recurrent and/or metastatic colorectal carcinoma (CRC) refractory to previous chemotherapy have been treated with levofolinic acid (I-FA) 100 mg/m2 i.v. over 1 h infusion followed by 5-fluorouracil (5-FU) 600 mg/m2 i.v. bolus every week for 6 weeks followed by a 2 week interval. Patients also received rIL-2 s.c. at 3 MU daily from day 1 to day 5 of each week for at least four consecutive weeks per cycle. Enrolled patients were divided in two groups: (i) group 1 including patients with progressive tumor refractory to chemotherapy with I-FA + 5-FU given for metastatic disease and (ii) group 2 consisting of patients with diagnosis of metastatic disease within 3 months from the completion of adjuvant chemotherapy with 5-FU + levamisole (LEV) after primary surgery. No objective response was observed in the group of 11 patients with CRC resistant to previous I-FA + 5-FU, thus no further patient with progressive disease after I-FA + 5-FU was included in the trial. In the group of patients pretreated with 5-FU + LEV, four patients experienced a PR with a mean duration of 7.3 months (range > or = 4.0-8.6) for an overall response rate of 18% (95% CI 12-26%). A stabilization of disease was observed in five cases (23%) with a mean duration of > or = 5.6 months (range > or = 2.0-7.0). The remaining 13 patients progressed. No complete responses were achieved. The mean overall survival was > or = 9.5 months (range > or = 2.0-14.0). Toxicity was generally mild. This study demonstrates that the combination of s.c. rIL-2 and intravenous 5-FU + I-FA on a weekly schedule may be safely given to patients with metastatic CRC on an outpatients basis. The addition of low-dose rIL-2 does not modify the toxicity profile of 5-FU + I-FA, even if IL-2-related side-effects such as systemic symptoms or cardiac abnormalities are to be expected. The clinical activity of the combination is not good, at least in terms of response rate, even if the duration of partial responses may suggest to test rIL-2 in a prospective study with response duration and overall survival as the final end-points.

Oral granisetron with or without methylprednisolone versus metoclopramide plus methylprednisolone in the management of delayed nausea and vomiting induced by cisplatin-based chemotherapy. A prospective randomized trial.

BACKGROUND: A single-institution, randomized open trial was prospectively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin-based chemotherapy. The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy. METHODS: All patients were treated with chemotherapeutic regimens containing cisplatin greater than or equal to 80 mg/m2 and received antiemetic therapy with granisetron 3 mg intravenously for the control of acute emesis. Patients who responded to treatment during the first 24 hours were randomized to receive (1) metoclopramide (0.5 mg/kg) intramuscularly three times daily plus methylprednisolone (125 mg) intramuscularly once a day or (2) granisetron (1 mg) orally twice daily or (3) oral granisetron (1 mg) orally plus methylprednisolone (125 mg) intramuscularly from days 2 to 5. RESULTS: Of the patients treated with metoclopramide plus methylprednisolone (n = 92), 53% had complete protection from delayed emesis, 16% a major response, 15% a minor response, and 15% no response. Of the patients treated with granisetron alone (n = 84), 33% had a complete response, 21% a major response, 23% a minor response, and 21% no response. In the patients treated with orally administered granisetron plus intramuscularly administered methylprednisolone (n = 86), 47% had a complete response, 17% a major response, 23% a minor response, and 13% no response. These differences reached statistical significance only when the complete response rate achieved in the metoclopramide plus methylprednisolone group was compared with that recorded in the oral granisetron group (P = 0.012). Moreover, the metoclopramide plus methylprednisolone and the orally administered granisetron plus corticosteroid arms were superior to the orally administered granisetron alone arm in preventing nausea (P < 0.038 and P < 0.002, respectively). No extrapyramidal side effects were noted for the granisetron alone and the granisetron plus methylprednisolone arms, whereas 6% of patients treated with metoclopramide had extrapyramidal adverse effects. Headache was recorded in 8% of patients treated with granisetron alone, in 9% treated with granisetron plus methylprednisolone, and in 3% treated with metoclopramide plus methylprednisolone. CONCLUSIONS: These data suggest that orally administered granisetron with or without methylprednisolone may be given safely to patients with cancer as prophylactic therapy against delayed emesis after high dose cisplatin therapy. Orally administered granisetron alone was less active than a standard combination of metoclopramide plus methylprednisolone. However, the addition of corticosteroid to orally administered granisetron improved the control of delayed emesis. The efficacy of the combination of metoclopramide plus methylprednisolone and oral granisetron with or without methylprednisolone against delayed emesis still is not entirely satisfactory.